27 10.2217/14796678.5.1.27 © 2009 Future Medicine ISSN 1479-6678 Future Cardiol. (2009) 5(1), 27–41 part of Future Cardiology Review NSTEACS versus STEMI: a more complex clinical syndrome Two-thirds of the hospital admissions with an acute coronary syndrome (ACS) present with- out persistent ST-segment elevation (NSTE) on the electrocardiogram [1] . Compared with patients showing ST-segment elevation (STE), those with NSTEACS are older and more fre- quently female, they have higher incidences of diabetes and chronic kidney dysfunction and they have a longer history of coronary artery disease, including previous myocardial infarc- tions (MI) and coronary revascularizations [1,2] ; their coronary arteries reflect these characteris- tics and show a higher prevalence of multivessel disease [2] . In more than 90% of the ST-segment eleva- tion myocardial infarction (STEMI) cases, an acutely occluded major coronary artery is evident; therefore, immediate reperfu- sion therapy is mandatory, using the fastest available strategy in order to limit irrevers- ible myocardial damage [3] . This strategy has been evidence based for 20 years with fibrin- olytic therapy [4] and became more effective with primary angioplasty [5] . The long-term follow-up of reperfusion studies have consis- tently demonstrated the long-lasting benefit of pharmacological [6] and mechanical single-shot intervention [7] . On the other end, NSTEACS represent a more complex clinical challenge, and only recently a clear evidence has been proved that an aggressive pharmaco-interven- tional approach provides long-term benefit when applied to higher-risk patients [8–13] . As shown in BOX 1, the reasons for this greater complexity are multifactorial. In-hospital mortality of STEMI patients is approximately twice as high as that seen in NSTEACS [1] and it is almost exclusively attributable to ventricular arrhythmias and cardiogenic shock or mechanical complica- tions owing to abrupt coronary occlusion. Improvements in the logistics, pharmacology and technology of early reperfusion have led to the recent dramatic reduction in STEMI mortality. For example, in-hospital mortal- ity decreased from 8.4% in 2000 to 4.6% in 2005 in the Global Registry of Acute Coronary Events (GRACE) registry [1] , and from 16% in 2002 to 9.5% in 2004 in the Vienna regis- try [14] . On the other hand, owing to the lesser impact of acute coronary occlusion, in-hospital mortality is lower in NSTEACS (less than 3% in the GRACE registry [1]), but owing to an older age of the patients and the more exten- sive atherosclerotic burden, ischemic recurren- cies and long-term mortality are worse com- pared with STEMI and, so far, have been less susceptible of significant improvements. Target populations and relevant therapeutic end points to further improve outcomes in NSTEACS patients Stefano Savonitto † , Nuccia Morici, Alice Sacco & Silvio Klugmann † Author for correspondence: Dipartimento Cardiologico ‘Angelo De Gasperis’, Ospedale Niguarda Ca’ Granda, Piazza Ospedale Maggiore 3, 20162 Milano, Italy n Tel.: +39 335 605 6565 n Fax: +39 026 444 2458 n stefano.savonitto@fastwebnet.it An aggressive pharmaco-interventional approach has been shown to improve long-term outcome among high-risk patients with acute coronary syndromes without ST-segment elevation (NSTEACS). However, these patients continue to represent a minority among those enrolled in clinical trials, thus precluding the possibility to further improve therapeutic efficacy. Target populations that are not adequately addressed by the majority of therapeutic trials are mainly the elderly and those with reduced renal function, who all show unfavorable outcome after an episode of NSTEACS. In order to allow comparison among different studies, a prerequisite for the planning of meaningful trials should be a uniform definition of the study end points besides mortality, particularly with reference to recurrent myocardial infarction, and rehospitalization owing to cardiovascular instability or severe bleeding. In addition to trial design issues, improvements in the regulatory rules for drug development and in hospital networking conceal significant opportunities to improve treatment of NSTEACS. Keywords n acute coronary syndromes n bleeding n myocardial infarction n outcome n treatment